Cefpirome and cefepime possess a greater antibacterial spectrum in vitro than third-generation cephalosporins because they are active against Enterobacteriaceae, which produce beta-lactamases, which may inactivate third-generation cephalosporins. The aim of this study was to quantitatively compare the in vitro activity of cefpirome and cefepime against Klebsiella spp. isolates. We have studied 342 Klebsiella spp. clinical isolates, from some hospitals in Eastern Romania. Minimum inhibitory concentrations (MICs) were determined by the dilution method in Mueller-Hinton agar. The mean MIC of sensitive population by cefpirome and cefepime was 1 mg/l, eight fold lower than breakpoint for susceptibility. The cefpirome and cefepime MICs remained below the proposed breakpoints for sensitivity of 8 mg/l for more 60% of strains. Mean "S" (mean MIC of the fully sensitive strains) is a very good indicator of the drug activity. Cefpirome and cefepime are active fourth-generation cephalosporins against clinical isolates of Klebsiella spp.